肾内血管紧张素系统在2型糖尿病大鼠的肾脏发育中异常活化的机制  

Aberrant Activation of Intrarenal Renin-angiotensin System during Kidney Development in Type 2 Diabetic Rats

作　　者：孙永新[1] 范愈燕[2,3] 支楠[3] 西山成[2] 刘雅[2] 黄雯[4] 姚丽[5] 

机构地区：[1]中国医科大学附属第一医院康复科,沈阳110001 [2]香川大学医学部药理科 [3]首都医科大学北京同仁医院传统医学科,北京100730 [4]首都医科大学北京同仁医院肾脏内科,北京100730 [5]中国医科大学附属第一医院肾脏内科,沈阳110001

出　　处：《中国医科大学学报》2012年第10期865-869,共5页Journal of China Medical University

基　　金：国家自然科学基金主任基金资助项目(81141040)

摘　　要：目的明确在糖尿病OLETF大鼠模型的肾脏发育中肾内血管紧张素系统(RAS)的活性作用。方法测定雄性糖尿病OLETF大鼠和正常LETO大鼠出生后第1、5、14天及第4~30周时,肾内血管紧张素Ⅱ(AngⅡ)的含量和RAS系统各组成成分的mRNA水平。结果正常LETO大鼠和糖尿病OLETF大鼠中,AngⅡ含量在出生后第1天达到高峰,在断奶期前后(出生后1 d^4周)随着年龄的增长而逐渐下降。在出生后1 d^4周龄期间,肾脏AngⅡ的含量和RAS组成成分的基因表达2组动物比较差异无统计学意义(P>0.05)。正常LETO大鼠肾内AngⅡ水平在青春期(7~11周龄)逐渐下降,然而糖尿病OLETF大鼠肾内AngⅡ水平在此期间无下降趋势,包括尿中血管紧张素原排泄率。糖尿病OLETF大鼠肾内血管紧张素原和肾素的mRNA水平明显高于正常LETO大鼠(P<0.05),2组比较血糖的差异无统计学意义(P>0.05)。结论糖尿病OLETF大鼠在青春期缺乏维持肾内低水平AngⅡ的发育缺陷是导致肾内AngⅡ异常升高的重要原因。Objective To define the precise patterns of intrarenal renin-angiotensin system（RAS） activities during kidney development in OLETF rats.Methods AngiotensinⅡ（Ang Ⅱ） contents and mRNA levels of RAS components were measured in male OLETF and control LETO rats at postnatal 1,5,14 days and 4-30 weeks of age.Results In both LETO and OLETF rats,kidney Ang Ⅱ levels hit the peak at one day postnatal and decreased age-dependently during the pre-and post-weaning periods.During the pre-and post-weaning periods（1 day-4 weeks）,Ang Ⅱ levels and gene expression of RAS components,including angiotensinogen（AGT）,renin and angiotensin-converting enzyme were not different between the animals（P 0.05）.In LETO rats,kidney Ang Ⅱ levels further decreased during puberty（from 7 to 11 weeks of age）,whereas no further age-dependent decline was observed in the kidney Ang Ⅱ levels in OLETF rats during puberty.At 11 weeks of age,kidney Ang Ⅱ levels,urinary excretion rate of AGT,and mRNA levels of AGT and renin were higher in OLETF than in LETO rats（P 0.05）,while no difference was observed of the blood glucose levels between the animals.Conclusion These data indicated that a lack of proper reduction in intrarenal Ang Ⅱ during pubescent may contribute to the onset and development of diabetic nephropathy in their later life.

关 键 词：血管紧张素 肾脏的发育 糖尿病 血管紧张素原 

分 类 号：R692[医药卫生—泌尿科学]